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Abstract Dynamic contrast-enhanced MRI (DCE-MRI) is increasingly used to non-invasively image blood-brain barrier leakage, yet its clinical utility has been hampered by issues such as noise and partial volume artifacts. In this retrospective study involving 306 adult patients with diffuse glioma, we applied deep learning-based super-resolution and denoising (DLSD) techniques to enhance the signal-to-noise ratio (SNR) and resolution of DCE-MRI. Quantitative analysis comparing standard DCE-MRI (std-DCE) and DL-enhanced DCE-MRI (DL-DCE) revealed that DL-DCE achieved significantly higher SNR and contrast-to-noise ratio (CNR) compared to std-DCE (SNR, 52.09 vs 27.21; CNR, 9.40 vs 4.71; P < 0.001 for all). Diagnostic performance assessed by the area under the receiver operating characteristic curve (AUROC) showed improved differentiation of WHO grades based on a pharmacokinetic parameter $$\hbox {V}_{{e}}$$ (AUC, 0.88 vs 0.83, P = 0.02), while remaining comparable to std-DCE in other parameters. Analysis of arterial input function (AIF) reliability demonstrated that $$\hbox {AIF}_{{DL}}$$ exhibited superior agreement compared to $$\hbox {AIF}_{{std}}$$ , as indicated by mostly higher intraclass correlation coefficients (Time to peak, 0.79 vs 0.43, P < 0.001). In conclusion, DLSD significantly enhances both the image quality and reliability of DCE-MRI in patients with diffuse glioma, while maintaining or improving diagnostic performance.

Abstract Local recurrences in patients with grade 4 adult-type diffuse gliomas mostly occur within residual non-enhancing T2 hyperintensity areas after surgical resection. Unfortunately, it is challenging to distinguish non-enhancing tumors from edema in the non-enhancing T2 hyperintensity areas using conventional MRI alone. Quantitative DCE MRI parameters such as Ktrans and Ve convey permeability information of glioblastomas that cannot be provided by conventional MRI. We used the publicly available nnU-Net to train a deep learning model that incorporated both conventional and DCE MRI to detect the subtle difference in vessel leakiness due to neoangiogenesis between the non-recurrence area and the local recurrence area, which contains a higher proportion of high-grade glioma cells. We found that the addition of Ve doubled the sensitivity while nonsignificantly decreasing the specificity for prediction of local recurrence in glioblastomas, which implies that the combined model may result in fewer missed cases of local recurrence. The deep learning model predictive of local recurrence may enable risk-adapted radiotherapy planning in patients with grade 4 adult-type diffuse gliomas.

Abstract Distortion of echo planar imaging (EPI) can be corrected using B0 field maps, which can be estimated with the topup algorithm that requires two EPI images with opposite distortions. In this study, we propose a new algorithm, termed topup algorithm by single K-space (TASK), to generate two input images from a single k-space for the topup algorithm to correct EPI distortions. The centric EPI contains the opposite phase-encoding polarities in one k-space, which can be divided into two halves with opposite distortions. Therefore, two inputs could be extracted by dividing the k-space into halves and processing them using the proposed procedure including an iterative procedure of automatic brain masking and uniformity correction. The efficiency of TASK was evaluated using 3D EPI. Quantitative evaluations showed that TASK corrected EPI distortion at a similar level to the traditional methods. The estimated field maps from the conventional topup and TASK showed a high correlation ( $$r=0.80\pm 0.05$$ r = 0.80 ± 0.05 ). An ablation study showed the validity of every suggested step. Furthermore, it was confirmed that TASK was effective for distortion correction of two-shot centric EPI as well, demonstrating its wider applicability. In conclusion, TASK can correct EPI distortions by its own single k-space information with no additional scan.

Abstract Adult-type diffuse glioma (grade 4) has infiltrating nature, and therefore local progression is likely to occur within surrounding non-enhancing T2 hyperintense areas even after gross total resection of contrast-enhancing lesions. Cerebral blood volume (CBV) obtained from dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) is a parameter that is well-known to be a surrogate marker of both histologic and angiographic vascularity in tumors. We built two nnU-Net deep learning models for prediction of early local progression in adult-type diffuse glioma (grade 4), one using conventional MRI alone and one using multiparametric MRI, including conventional MRI and DSC-PWI. Local progression areas were annotated in a non-enhancing T2 hyperintense lesion on preoperative T2 FLAIR images, using the follow-up contrast-enhanced (CE) T1-weighted (T1W) images as the reference standard. The sensitivity was doubled with the addition of nCBV (80% vs. 40%, P = 0.02) while the specificity was decreased nonsignificantly (29% vs. 48%, P = 0.39), suggesting that fewer cases of early local progression would be missed with the addition of nCBV. While the diagnostic performance of CBV model is still poor and needs improving, the multiparametric deep learning model, which presumably learned from the subtle difference in vascularity between early local progression and non-progression voxels within perilesional T2 hyperintensity, may facilitate risk-adapted radiotherapy planning in adult-type diffuse glioma (grade 4) patients.

Objectives Using tissue-engineered materials for esophageal reconstruction is a technically challenging task in animals that requires bioreactor training to enhance cellular reactivity. There have been many attempts at esophageal tissue engineering, but the success rate has been limited due to difficulty in initial epithelialization in the special environment of peristalsis. The purpose of this study was to evaluate the potential of an artificial esophagus that can enhance the regeneration of esophageal mucosa and muscle through the optimal combination of a double-layered polymeric scaffold and a custom-designed mesenchymal stem cell-based bioreactor system in a canine model. Methods We fabricated a novel double-layered scaffold as a tissue-engineered esophagus using an electrospinning technique. Prior to transplantation, human-derived mesenchymal stem cells were seeded into the lumen of the scaffold, and bioreactor cultivation was performed to enhance cellular reactivity. After 3 days of cultivation using the bioreactor system, tissue-engineered artificial esophagus was transplanted into a partial esophageal defect (5×3 cm-long resection) in a canine model. Results Scanning electron microscopy (SEM) showed that the electrospun fibers in a tubular scaffold were randomly and circumferentially located toward the inner and outer surfaces. Complete recovery of the esophageal mucosa was confirmed by endoscopic analysis and SEM. Esophagogastroduodenoscopy and computed tomography also showed that there were no signs of leakage or stricture and that there was a normal lumen with complete epithelialization. Significant regeneration of the mucosal layer was observed by keratin-5 immunostaining. Alpha-smooth muscle actin immunostaining showed significantly greater esophageal muscle regeneration at 12 months than at 6 months. Conclusion Custom-designed bioreactor cultured electrospun polyurethane scaffolds can be a promising approach for esophageal tissue engineering.

Abstract The clearance pathways of brain waste products in humans are still under debate in part due to the lack of noninvasive imaging techniques for meningeal lymphatic vessels (mLVs). In this study, we propose a new noninvasive mLVs imaging technique based on an inter-slice blood perfusion MRI called alternate ascending/descending directional navigation (ALADDIN). ALADDIN with inversion recovery (IR) at single inversion time of 2300 ms (single-TI IR-ALADDIN) clearly demonstrated parasagittal mLVs around the human superior sagittal sinus (SSS) with better detectability and specificity than the previously suggested noninvasive imaging techniques. While in many studies it has been difficult to detect mLVs and confirm their signal source noninvasively, the detection of mLVs in this study was confirmed by their posterior to anterior flow direction and their velocities and morphological features, which were consistent with those from the literature. In addition, IR-ALADDIN was compared with contrast-enhanced black blood imaging to confirm the detection of mLVs and its similarity. For the quantification of flow velocity of mLVs, IR-ALADDIN was performed at three inversion times of 2000, 2300, and 2600 ms (three-TI IR-ALADDIN) for both a flow phantom and humans. For this preliminary result, the flow velocity of the dorsal mLVs in humans ranged between 2.2 and 2.7 mm/s. Overall, (i) the single-TI IR-ALADDIN can be used as a novel non-invasive method to visualize mLVs in the whole brain with scan time of ~ 17 min and (ii) the multi-TI IR-ALADDIN can be used as a way to quantify the flow velocity of mLVs with a scan time of ~ 10 min (or shorter) in a limited coverage. Accordingly, the suggested approach can be applied to noninvasively studying meningeal lymphatic flows in general and also understanding the clearance pathways of waste production through mLVs in humans, which warrants further investigation.

Abstract This study aimed to find any ambiguous genetic outlier for “oligodendroglioma, IDH-mutant and 1p/19q-codeleted (O_IDH_mut)” and “astrocytoma, IDH-mutant (A_IDH_mut)” and to redefine the genetic landscape and prognostic factors of IDH-mutant gliomas. Next-generation sequencing (NGS) using a brain tumor-targeted gene panel, methylation profiles, and clinicopathological features were analyzed for O_IDH_mut (n = 74) in 70 patients and for A_IDH_mut (n = 95) in 90 patients. 97.3% of O_IDH_mut and 98.9% of A_IDH_mut displayed a classic genomic landscape. Combined CIC (75.7%) and/or FUBP1 (45.9%) mutations were detected in 93.2% and MGMTp methylation in 95.9% of O_IDH_mut patients. In A_IDH_mut, TP53 mutations were found in 86.3% and combined ATRX (82.1%) and TERTp (6.3%) mutations in 88.4%. Although there were 3 confusing cases, NOS (not otherwise specified) category, based on genetic profiles, but they were clearly classified by combining histopathology and DKFZ methylation classifier algorithms. The patients with MYCN amplification and/or CDKN2A/2B homozygous deletion in the A_IDH_mut category had a worse prognosis than those without these gene alterations and MYCN-amplified A_IDH_mut showed the worst prognosis. However, there was no prognostic genetic marker in O_IDH_mut. In histopathologically or genetically ambiguous cases, methylation profiles can be used as an objective tool to avoid a diagnosis of NOS or NEC (not elsewhere classified), as well as for tumor classification. The authors have not encountered a case of true mixed oligoastrocytoma using an integrated diagnosis of histopathological, genetic and methylation profiles. MYCN amplification, in addition to CDKN2A/2B homozygous deletion, should be included in the genetic criteria for CNS WHO grade 4 A_IDH_mut.

Abstract Acute intracranial haemorrhage (AIH) is a potentially life-threatening emergency that requires prompt and accurate assessment and management. This study aims to develop and validate an artificial intelligence (AI) algorithm for diagnosing AIH using brain-computed tomography (CT) images. A retrospective, multi-reader, pivotal, crossover, randomised study was performed to validate the performance of an AI algorithm was trained using 104,666 slices from 3010 patients. Brain CT images (12,663 slices from 296 patients) were evaluated by nine reviewers belonging to one of the three subgroups (non-radiologist physicians, n = 3; board-certified radiologists, n = 3; and neuroradiologists, n = 3) with and without the aid of our AI algorithm. Sensitivity, specificity, and accuracy were compared between AI-unassisted and AI-assisted interpretations using the chi-square test. Brain CT interpretation with AI assistance results in significantly higher diagnostic accuracy than that without AI assistance (0.9703 vs. 0.9471, p

Abstract Purpose Primary central nervous system lymphoma (PCNSL) is an uncommon extranodal non‐Hodgkin's lymphoma. Here, the feasibility of nuclear magnetic resonance (NMR) metabolomics for the diagnosis and prognosis prediction of PCNSL, as well as its correlation with magnetic resonance imaging (MRI) characteristics, was assessed. Patients and Methods Cerebrospinal fluid (CSF) samples from PCNSL and normal groups (n = 41 for each) were obtained along with MRI data including pre‐ and postcontrast as well as T1‐, T2‐, and diffusion‐weighted imaging for the treatment‐naïve PCNSL patients (n = 24). The CSF samples were analyzed using nuclear magnetic resonance (NMR). Results The CSF NMR metabolomic exhibited clear differences with a diagnostic sensitivity of 100% and a specificity of 97.6%. The citrate level of the leptomeningeal enhancement (LE) (+) group was significantly lower than that of the LE (−) group (p = 0.018). In addition, the MRI apparent diffusion coefficient (ADC) value of the tumor was positively correlated with the glucose level (p = 0.025). However, none of the marker metabolites were significant prognosis predictors in univariate analysis. Conclusions In conclusion, the NMR metabolomics could be helpful to diagnose PCNSL, but not for the prognosis, and MRI features (LE or ADC) can reflect the metabolic profiles of PCNSL.

This study aimed to optimize velocity-selective magnetic resonance angiography (VS-MRA) protocols for whole-neck angiography and demonstrate its feasibility in healthy subjects with comparisons to clinical 3D time-of-flight (TOF) angiography. To help optimize VS-MRA protocols, 2D phase-contrast (PC) flow imaging and 3D B0 and B1 field mappings were performed on five healthy volunteers. Based on these measurements, a slab-selective (SS) inversion preparation was applied prior to a VS saturation preparation to further suppress venous blood, while the VS preparation pulse was designed with compensation for field offsets. VS-MRA and 3D TOF were performed on six healthy subjects, and relative contrast ratios (CRs) between artery and muscle signals were calculated for twenty arterial regions for comparisons. The pre-compensated VS pulse improved the visualization of the subclavian arteries and suppression of background tissues, which involved large B0 and B1 field errors. The combination of SS and VS preparations effectively suppressed venous blood. While the relative CR values were 0.78 ± 0.08 and 0.72 ± 0.10 for VS-MRA and 3D TOF, respectively, over the twenty segments, VS-MRA outperformed 3D TOF in visualizing arterial segments of a small size or with a horizontal orientation, such as subclavian, facial, and occipital arteries. The proposed neck VS-MRA with the field-error-compensated VS preparation combined with the SS preparation is feasible and superior to 3D TOF in visualizing small and/or horizontally oriented arterial segments.

According to the new 2021 World Health Organization (WHO) classification of tumors of the central nervous system (CNS) the classification of the primary intramedullary spinal cord tumors (IM-SCT) follows that of CNS tumors. However, since the genetics and methylation profile of ependymal tumors depend on the location of the tumor, the ‘spinal (SP)’ should be added for the ependymoma (EPN) and subependymoma (SubEPN). For an evidence-based review, the authors reviewed SCTs in the archives of the Seoul National University Hospital over the past decade. The frequent pathologies of primary IM-SCT were SP-EPN (45.1%), hemangioblastoma (20.0%), astrocytic tumors (17.4%, including pilocytic astrocytoma [4.6%] and diffuse midline glioma, H3 K27-altered [4.0%]), myxopapillary EPN (11.0%), and SP-subEPN (3.0%) in decreasing order. IDH-mutant astrocytomas, oligodendrogliomas, glioneuronal tumors, embryonal tumors, and germ cell tumors can occur but are extremely rare in the spinal cord. Genetic studies should support for the primary IM-SCT classification. In the 2021 WHO classifications, extramedullary SCT did not change significantly but contained several new genetically defined types of mesenchymal tumors. This article focused on primary IM-SCT for tumor frequency, age, sex difference, pathological features, and genetic abnormalities, based on a single-institute experience.

Abstract Background The activation of the telomere maintenance mechanism (TMM) is one of the critical drivers of cancer cell immortality. In gliomas, TERT expression and TERT promoter mutation are considered to reliably indicate telomerase activation, while ATRX mutation and/or loss indicates an alternative lengthening of telomeres (ALT). However, these relationships have not been extensively validated in tumor tissues. Methods Telomerase repeated amplification protocol (TRAP) and C-circle assays were used to profile and characterize the TMM cross-sectionally (n = 412) and temporally (n = 133) across glioma samples. WES, RNA-seq, and NanoString analyses were performed to identify and validate the genetic characteristics of the TMM groups. Results We show through the direct measurement of telomerase activity and ALT in a large set of glioma samples that the TMM in glioma cannot be defined solely by the combination of telomerase activity and ALT, regardless of TERT expression, TERT promoter mutation, and ATRX loss. Moreover, we observed that a considerable proportion of gliomas lacked both telomerase activity and ALT. This telomerase activation-negative and ALT negative group exhibited evidence of slow growth potential. By analyzing a set of longitudinal samples from a separate cohort of glioma patients, we discovered that the TMM is not fixed and can change with glioma progression. Conclusions This study suggests that the TMM is dynamic and reflects the plasticity and oncogenicity of tumor cells. Direct measurement of telomerase enzyme activity and evidence of ALT should be considered when defining TMM. An accurate understanding of the TMM in glioma is expected to provide important information for establishing cancer management strategies.

Abstract Cancer immunotherapy has emerged as a novel cancer treatment, although recent immunotherapy trials have produced suboptimal outcomes, with durable responses seen only in a small number of patients. The tumor microenvironment (TME) has been shown to be responsible for tumor immune escape and therapy failure. The vital component of the TME is tumor-associated macrophages (TAMs), which are usually associated with poor prognosis and drug resistance, including immunotherapies, and have emerged as promising targets for cancer immunotherapy. Recently, nanoparticles, because of their unique physicochemical characteristics, have emerged as crucial translational moieties in tackling tumor-promoting TAMs that amplify immune responses and sensitize tumors to immunotherapies in a safe and effective manner. In this review, we mainly described the current potential nanomaterial-based therapeutic strategies that target TAMs, including restricting TAMs survival, inhibiting TAMs recruitment to tumors and functionally repolarizing tumor-supportive TAMs to antitumor type. The current understanding of the origin and polarization of TAMs, their crucial role in cancer progression and prognostic significance was also discussed in this review. We also highlighted the recent evolution of chimeric antigen receptor (CAR)-macrophage cell therapy.

Abstract Temporal and spatial resolution of dynamic contrast-enhanced MR imaging (DCE-MRI) is critical to reproducibility, and the reproducibility of high-resolution (HR) DCE-MRI was evaluated. Thirty consecutive patients suspected to have brain tumors were prospectively enrolled with written informed consent. All patients underwent both HR-DCE (voxel size, 1.1 × 1.1 × 1.1 mm3; scan interval, 1.6 s) and conventional DCE (C-DCE; voxel size, 1.25 × 1.25 × 3.0 mm3; scan interval, 4.0 s) MRI. Regions of interests (ROIs) for enhancing lesions were segmented twice in each patient with glioblastoma (n = 7) to calculate DCE parameters (Ktrans, Vp, and Ve). Intraclass correlation coefficients (ICCs) of DCE parameters were obtained. In patients with gliomas (n = 25), arterial input functions (AIFs) and DCE parameters derived from T2 hyperintense lesions were obtained, and DCE parameters were compared according to WHO grades. ICCs of HR-DCE parameters were good to excellent (0.84–0.95), and ICCs of C-DCE parameters were moderate to excellent (0.66–0.96). Maximal signal intensity and wash-in slope of AIFs from HR-DCE MRI were significantly greater than those from C-DCE MRI (31.85 vs. 7.09 and 2.14 vs. 0.63; p

Purpose To explore cerebrovascular reservoir (CVR) and arterial transit time (ATT) changes using acetazolamide-challenged multi-phase arterial spin labeling (MP-ASL) perfusion-weighted MRI in chronic cerebrovascular steno-occlusive disease. Materials and Methods This retrospective study enrolled patients with chronic steno-occlusion who underwent acetazolamide-challenged MP-ASL between June 2019 and October 2020. Cerebral blood flow, CVR, basal ATT, and ATT changes associated with severe stenosis, total occlusion, and chronic infarction lesions were compared. Results There were 32 patients (5 with bilateral steno-occlusion) in our study sample. The CVR was significantly reduced during total occlusion compared with severe stenosis (26.2% ± 28.8% vs. 41.4% ± 34.1%, respectively, p = 0.004). The ATT changes were not significantly different (p = 0.717). The CVR was marginally lower in patients with chronic infarction (29.6% ± 39.1% vs. 38.9% ± 28.7%, respectively, p = 0.076). However, the ATT was less shortened in patients with chronic infarction (-54 ± 135 vs. -117 ± 128 ms, respectively, p = 0.013). Conclusion Acetazolamide-challenged MP-ASL provides an MRI-based CVR evaluation tool for chronic steno-occlusive disease.

Abstract Glioblastoma remains the most devastating brain tumor despite optimal treatment, because of the high rate of recurrence. Distant recurrence has distinct genomic alterations compared to local recurrence, which requires different treatment planning both in clinical practice and trials. To date, perfusion-weighted MRI has revealed that perfusional characteristics of tumor are associated with prognosis. However, not much research has focused on recurrence patterns in glioblastoma: namely, local and distant recurrence. Here, we propose two different neural network models to predict the recurrence patterns in glioblastoma that utilizes high-dimensional radiomic profiles based on perfusion MRI: area under the curve (AUC) (95% confidence interval), 0.969 (0.903–1.000) for local recurrence; 0.864 (0.726–0.976) for distant recurrence for each patient in the validation set. This creates an opportunity to provide personalized medicine in contrast to studies investigating only group differences. Moreover, interpretable deep learning identified that salient radiomic features for each recurrence pattern are related to perfusional intratumoral heterogeneity. We also demonstrated that the combined salient radiomic features, or “radiomic risk score”, increased risk of recurrence/progression (hazard ratio, 1.61; p = 0.03) in multivariate Cox regression on progression-free survival.

Abstract Introduction This study aimed to investigate alterations in whole‐brain functional connectivity after a concussion using graph‐theory analysis from global and local perspectives and explore the association between changes in the functional network properties and cognitive performance. Methods Individuals with mild traumatic brain injury (mTBI, n = 29) within a month after injury, and age‐ and sex‐matched healthy controls (n = 29) were included. Graph‐theory measures on functional connectivity assessed using resting state functional magnetic resonance imaging data were acquired from each participant. These included betweenness centrality, strength, clustering coefficient, local efficiency, and global efficiency. Multi‐domain cognitive functions were correlated with the graph‐theory measures. Results In comparison to the controls, the mTBI group showed preserved network characteristics at a global level. However, in the local network, we observed decreased betweenness centrality, clustering coefficient, and local efficiency in several brain areas, including the fronto‐parietal attention network. Network strength at the local level showed mixed‐results in different areas. The betweenness centrality of the right parahippocampus showed a significant positive correlation with the cognitive scores of the verbal learning test only in the mTBI group. Conclusion The intrinsic functional connectivity after mTBI is preserved globally, but is suboptimally organized locally in several areas. This possibly reflects the neurophysiological sequelae of a concussion. The present results may imply that the network property could be used as a potential indicator for clinical outcomes after mTBI.

There is a need to further improve the efficacy of biodegradable wafers used in surgically treated brain tumors. Here, the authors report a flexible, biodegradable wireless device capable of adhesion to surgical site for optimal drug delivery upon mild-thermic actuation and report therapeutic efficacy in mouse and canine tumor models.

PurposeTo assess glioblastoma multiforme (GBM) formation with similar imaging characteristics to human GBM using multiparametric magnetic resonance imaging (MRI) in an orthotopic xenograft canine GBM model.Materials and methodsThe canine GBM cell line J3T1 was subcutaneously injected into 6-week-old female BALB/c nude mice to obtain tumour fragments. Tumour fragments were implanted into adult male mongrel dog brains through surgery. Multiparametric MRI was performed with conventional MRI, diffusion-weighted imaging, and dynamic susceptibility contrast-enhanced perfusion-weighted imaging at one week and two weeks after surgery in a total of 15 surgical success cases. The presence of tumour cells, the necrotic area fraction, and the microvessel density (MVD) of the tumour on the histologic specimen were assessed. Tumour volume, diffusion, and perfusion parameters were compared at each time point using Wilcoxon signed-rank tests, and the differences between tumour and normal parenchyma were compared using unpaired t-tests. Spearman correlation analysis was performed between the imaging and histologic parameters.ResultsAll animals showed a peripheral enhancing lesion on MRI and confirmed the presence of a tumour through histologic analysis (92.3%). The normalized perfusion values did not show significant decreases through at least 2 weeks after the surgery (P > 0.05). There was greater cerebral blood volume and flow in the GBM than in the normal-appearing white matter (1.46 ± 0.25 vs. 1.13 ± 0.16 and 1.30 ± 0.22 vs. 1.02 ± 0.14; P < 0.001 and P < 0.001, respectively). The MVD in the histologic specimens was correlated with the cerebral blood volume in the GBM tissue (r = 0.850, P = 0.004).ConclusionOur results suggest that the canine GBM model showed perfusion imaging characteristics similar to those of humans, and it might have potential as a model to assess novel technical developments for GBM treatment.

Background Mixed gliomas, such as oligoastrocytomas (OA), anaplastic oligoastrocytomas, and glioblastomas (GBMs) with an oligodendroglial component (GBMO) are defined as tumors composed of a mixture of two distinct neoplastic cell types, astrocytic and oligodendroglial. Recently, mutations ATRX and TP53, and codeletion of 1p/19q are shown to be genetic hallmarks of astrocytic and oligodendroglial tumors, respectively. Subsequent molecular analyses of mixed gliomas preferred the reclassification to either oligodendroglioma or astrocytoma. This study was designed to apply genetically integrated diagnostic criteria to mixed gliomas and determine usefulness and prognostic value of new classification in Korean patients. Methods Fifty-eight cases of mixed OAs and GBMOs were retrieved from the pathology archives of Seoul National University Hospital from 2004 to 2015. Reclassification was performed according to genetic and immunohistochemical properties. Clinicopathological characteristics of each subgroup were evaluated. Overall survival was assessed and compared between subgroups. Results We could reclassify all mixed OAs and GBMOs into either astrocytic or oligodendroglial tumors. Notably, 29 GBMOs could be reclassified into 11 cases of GBM, IDH-mutant, 16 cases of GBM, IDH-wildtype, and two cases of anaplastic oligodendroglioma, IDH mutant. Overall survival was significantly different among these new groups (p

Abstract Mutations in the telomerase reverse transcriptase gene promoter (TERTp) are common in glioblastomas (GBMs) and oligodendrogliomas (ODGs), and therefore, have a key role in tumorigenesis and may be of prognostic value. However, the extent of their prognostic importance in various gliomas is controversial. We studied 168 patients separated into five groups: Group 1: 65 patients with ODG carrying an IDH1 or IDH2 mutation (IDH-mutant) and 1p/19q–codeletion, Group 2: 23 patients with anaplastic astrocytoma (AA), IDH-mutant, Group 3: 13 patients with GBM, IDH-mutant, Group 4: 15 patients with AA, IDH-wildtype (WT), and Group 5: 52 patients with GBM, IDH-WT. TERTp mutations were found in 96.9%, 4.4%, 76.9%, 20.0%, and 84.6% of patients in Groups 1, 2, 3, 4, and 5, respectively. The R132H mutation in IDH1 was found in 60.5% (23/38) of patients in the AA cohort (Groups 2 and 4) and 20.0% (13/65) of patients from our GBM cohort (Groups 3 and 5), whereas all patients with ODG (Group 1) had a mutation either in IDH1 (n = 62) or IDH2 (n = 3). Using Kaplan Meier survival analysis, we found that the TERTp mutation was correlated with poor overall survival (OS) in Groups 2 and 4 combined (P = 0.001) and in Group 4 (P = 0.113), and in multivariate analysis, the TERTp mutant group was associated with significantly poor survival in Group 5 (P = 0.045). However, IDH mutation, MGMT methylation, and younger patient age (

This study evaluated the possibility of accelerated gadolinium accumulation in irradiated brain parenchyma where the blood-brain barrier was weakened.From January 2010 to June 2015, 44 patients with supratentorial glioblastoma were retrospectively identified who underwent pre- and post-radiation brain MR imaging, including R1 mapping. The mean dose of administered gadobutrol (Gadovist, Bayer, Germany) was 5.1 vials. Regions of interest (ROIs) were drawn around tumors that were located within 50-100% iso-dose lines of maximum radiation dose. ROIs were also drawn at globus pallidus, thalamus, and cerebral white matter. Averages of R1 values (unit: s-1) before and after radiation and those of R1 ratio (post-radiation R1 / pre-radiation R1) were compared by t-test or rank sum test as appropriate. Multiple linear regression analysis was performed to evaluate independent association factors for R1 value increase at irradiated parenchyma.The mean R1 values in peri-tumoral areas were significantly increased after radiotherapy (0.7901±0.0977 [mean±SD] vs. 0.8146±0.1064; P

Glioblastoma (GBM) with oligodendroglioma component (GBMO) is a newly described GBM subtype in the 2007 World Health Organization classification. However, its biological and genetic characteristics are largely unknown. We investigated the clinicopathological and molecular features of 34 GBMOs and compared the survival rate of these patients with those of patients with astrocytoma, oligodendroglioma, anaplastic oligoastrocytoma (AOA), and conventional GBMs in our hospital. GBMO could be divided into two groups based on the presence of an IDH1 mutation. The IDH1 mutation was more frequently found in secondary GBMO, which had lower frequencies of EGFR amplification but higher MGMT methylation than the wild type IDH1 group, and patients with mutant IDH1 GBMO were on average younger than those with wild-type IDH1. Therefore, GBMO is a clinically and molecularly heterogeneous subtype, largely belonging to a proneural and classical subtype of GBM. The survival rate of GBMO patients itself was worse than that of AOA patients but not significantly better than that of conventional GBM patients. GBMO survival was independent of the dominant histopathological subtype i.e., astrocyte-dominant or oligodendroglioma -dominant, but it was significantly associated with the IDH1 mutation and MGMT methylation status. Therefore, GBMO should be regarded as a separate entity from AOA and must be classified as a subtype of GBM. However, further study is needed to determine whether it is a pathologic variant or a pattern of GBM because GBMO has a similar prognosis to conventional GBMs.

This study aimed to explore the utility of arterial spin labeling perfusion-weighted imaging (ASL-PWI) in patients with suspected seizures in acute settings. A total of 164 patients who underwent ASL-PWI for suspected seizures in acute settings (with final diagnoses of seizure [n = 129], poststroke seizure [n = 18], and seizure mimickers [n = 17]), were included in this retrospective study. Perfusion abnormality was analyzed for: (1) pattern, (2) multifocality, and (3) atypical distribution against vascular territories. Perfusion abnormality was detected in 39% (50/129) of the seizure patients, most (94%, 47/50) being the hyperperfusion pattern. Of the patients with perfusion abnormality, multifocality or hemispheric involvement and atypical distribution against vascular territory were revealed in 46% (23/50) and 98% (49/50), respectively. In addition, seizures showed characteristic features including hyperperfusion (with or without non-territorial distribution) on ASL-PWI, thus differentiating them from poststroke seizures or seizure mimickers. In patients in whom seizure focus could be localized on both EEG and ASL-PWI, the concordance rate was 77%. The present study demonstrates that ASL-PWI can provide information regarding cerebral perfusion status in patients with seizures in acute settings and has the potential to be used as a non-invasive imaging tool to identify the cerebral perfusion in patients with seizures.

BACKGROUND AND PURPOSE:Arterial spin-labeling (ASL) was recently introduced as a noninvasive method to evaluate cerebral hemodynamics. The purposes of this study were to assess the ability of ASL imaging to detect crossed cerebellar diaschisis (CCD) in patients with their first unilateral supratentorial hyperacute stroke and to identify imaging or clinical factors significantly associated with CCD. MATERIALS AND METHODS:We reviewed 204 consecutive patients who underwent MRI less than 8 hours after the onset of stroke symptoms. The inclusion criteria were supratentorial abnormality in diffusion-weighted images in the absence of a cerebellar or brain stem lesion, bilateral supratentorial infarction, subacute or chronic infarction, and MR angiography showing vertebrobasilar system disease. For qualitative analysis, asymmetric cerebellar hypoperfusion in ASL images was categorized into 3 grades. Quantitative analysis was performed to calculate the asymmetric index (AI). The patients' demographic and clinical features and outcomes were recorded. Univariate and multivariate analyses were also performed. RESULTS:A total of 32 patients met the inclusion criteria, and 24 (75%) presented CCD. Univariate analyses revealed more frequent arterial occlusions, higher diffusion-weighted imaging (DWI) lesion volumes and higher initial NIHSS and mRS scores in the CCD-positive group compared with the CCD-negative group (all p < .05). The presence of arterial occlusion and the initial mRS scores were related with the AI (all p < .05). Multivariate analyses revealed that arterial occlusion and the initial mRS scores were significantly associated with CCD and AI. CONCLUSION:ASL imaging could detect CCD in 75% of patients with hyperacute infarction. We found that CCD was more prevalent in patients with arterial occlusion, larger ischemic brain volumes, and higher initial NIHSS and mRS scores. In particular, vessel occlusion and initial mRS score appeared to be significantly related with CCD pathophysiology in the hyperacute stage.

To assess the effect of computer-aided detection (CAD) of brain metastasis (BM) on radiologists' diagnostic performance in interpreting three-dimensional brain magnetic resonance (MR) imaging using follow-up imaging and consensus as the reference standard.The institutional review board approved this retrospective study. The study cohort consisted of 110 consecutive patients with BM and 30 patients without BM. The training data set included MR images of 80 patients with 450 BM nodules. The test set included MR images of 30 patients with 134 BM nodules and 30 patients without BM. We developed a CAD system for BM detection using template-matching and K-means clustering algorithms for candidate detection and an artificial neural network for false-positive reduction. Four reviewers (two neuroradiologists and two radiology residents) interpreted the test set images before and after the use of CAD in a sequential manner. The sensitivity, false positive (FP) per case, and reading time were analyzed. A jackknife free-response receiver operating characteristic (JAFROC) method was used to determine the improvement in the diagnostic accuracy.The sensitivity of CAD was 87.3% with an FP per case of 302.4. CAD significantly improved the diagnostic performance of the four reviewers with a figure-of-merit (FOM) of 0.874 (without CAD) vs. 0.898 (with CAD) according to JAFROC analysis (p < 0.01). Statistically significant improvement was noted only for less-experienced reviewers (FOM without vs. with CAD, 0.834 vs. 0.877, p < 0.01). The additional time required to review the CAD results was approximately 72 sec (40% of the total review time).CAD as a second reader helps radiologists improve their diagnostic performance in the detection of BM on MR imaging, particularly for less-experienced reviewers.

To analyze the enhancement patterns and apparent diffusion coefficient (ADC) values of non-measurable surgical cavity wall enhancement pattern, newly appearing after completion of standard concurrent chemoradiotherapy (CCRT) with temozolomide in glioblastoma patients for the prognosis prediction.From January 2010 to April 2014, among 190 patients with histopathologically confirmed glioblastoma, a total of 33 patients with non-measurable wall enhancement on post-CCRT MR imaging were enrolled and divided into two subgroups: non-progression (n = 18) and progression groups (n = 15). We analyzed the wall enhancement patterns, which were categorized into three patterns: thin, thick and nodular enhancement. ADC values were measured in the enhancing portions of the walls. The progression-free survival (PFS) related to the wall enhancement was analyzed by Kaplan-Meier analysis, and survival curves were compared using the log-rank test.Statistically significant differences in the surgical cavity wall enhancement patterns was shown between the progression and non-progression groups (P = 0.0032). Thin wall enhancement was more frequently observed in the non-progression group, and thick or nodular wall enhancement were observed in the progression group (P = 0.0016). There was no statistically significant difference in the mean ADC values between the progression and non-progression groups. The mean PFS was longer in patients with thin wall enhancement than in those with nodular or thick wall enhancement (35.5 months vs. 15.8 months, P = 0.008).Pattern analysis of non-measurable surgical cavity wall enhancement on post-CCRT MR imaging might be useful tool for predicting prognosis of GBM patient before clear progression of non-measurable disease.

Arterial cerebral blood volume (aCBV) is associated with many physiologic and pathologic conditions. Recently, multiphase balanced steady state free precession (bSSFP) readout was introduced to measure labeled blood signals in the arterial compartment, based on the fact that signal difference between labeled and unlabeled blood decreases with the number of RF pulses that is affected by blood velocity. In this study, we evaluated the feasibility of a new 2D inter-slice bSSFP-based arterial spin labeling (ASL) technique termed, alternate ascending/descending directional navigation (ALADDIN), to quantify aCBV using multiphase acquisition in six healthy subjects. A new kinetic model considering bSSFP RF perturbations was proposed to describe the multiphase data and thus to quantify aCBV. Since the inter-slice time delay (TD) and gap affected the distribution of labeled blood spins in the arterial and tissue compartments, we performed the experiments with two TDs (0 and 500 ms) and two gaps (300% and 450% of slice thickness) to evaluate their roles in quantifying aCBV. Comparison studies using our technique and an existing method termed arterial volume using arterial spin tagging (AVAST) were also separately performed in five subjects. At 300% gap or 500-ms TD, significant tissue perfusion signals were demonstrated, while tissue perfusion signals were minimized and arterial signals were maximized at 450% gap and 0-ms TD. ALADDIN has an advantage of visualizing bi-directional flow effects (ascending/descending) in a single experiment. Labeling efficiency (α) of inter-slice blood flow effects could be measured in the superior sagittal sinus (SSS) (20.8±3.7%.) and was used for aCBV quantification. As a result of fitting to the proposed model, aCBV values in gray matter (1.4-2.3 mL/100 mL) were in good agreement with those from literature. Our technique showed high correlation with AVAST, especially when arterial signals were accentuated (i.e., when TD = 0 ms) (r = 0.53). The bi-directional perfusion imaging with multiphase ALADDIN approach can be an alternative to existing techniques for quantification of aCBV.

Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) are frequently found in brain tumors, and the resulting onco-metabolite, 2-hydroxyglutarate (2HG), has been suggested to be a potential diagnostic and prognostic biomarker of the diseases. Indeed, recent studies have demonstrated the feasibility of non-invasively detecting 2HG by using proton magnetic resonance spectroscopy (1H-MRS). Due to severe spectral overlaps of 2HG with its background metabolites and spectral baselines, however, the majority of those previous studies employed spectral editing methods with long echo times (TEs) instead of the most commonly used short TE approach with spectral fitting. Consequently, the results obtained with spectral editing methods may potentially be prone to errors resulting from substantial signal loss due to relaxation. Given that the spectral region where the main signal of 2HG resides is particularly sensitive to spectral baseline in metabolite quantification, we have investigated the impact of incorporating voxel-specifically measured baselines into the spectral basis set on the performance of the conventional short TE approach in 2HG detection in rodent models (Fisher 344 rats; n = 19) of IDH1/2 mutant-overexpressing F98 glioma at 9.4T. Metabolite spectra were acquired (SPECIAL sequence) for a tumor region and the contralateral normal region of the brain for each animal. For the estimation of spectral baselines metabolite-nulled spectra were obtained (double-inversion-recovery SPECIAL sequence) for each individual voxels. Data were post-processed with and without the measured baselines using MRUI and LCModel-the two most widely used data post-processing packages. Our results demonstrate that in-vivo detection of 2HG using the conventional short TE approach is challenging even at 9.4T. However, incorporation of voxel-specifically measured spectral baselines may potentially improve its performance. Upon more thorough validation in a larger number of animals and more importantly in human patients, the potential utility of the proposed short TE acquisition with voxel-specific baseline measurement approach in 2HG detection may need to be considered in the study design.

To evaluate the diagnostic performance of cerebral blood flow (CBF) by using arterial spin labeling (ASL) perfusion magnetic resonance (MR) imaging to differentiate glioblastoma (GBM) from brain metastasis.The institutional review board of our hospital approved this retrospective study. The study population consisted of 128 consecutive patients who underwent surgical resection and were diagnosed as either GBM (n = 89) or brain metastasis (n = 39). All participants underwent preoperative MR imaging including ASL. For qualitative analysis, the tumors were visually graded into five categories based on ASL-CBF maps by two blinded reviewers. For quantitative analysis, the reviewers drew regions of interest (ROIs) on ASL-CBF maps upon the most hyperperfused portion within the tumor and upon peritumoral T2 hyperintensity area. Signal intensities of intratumoral and peritumoral ROIs for each subject were normalized by dividing the values by those of contralateral normal gray matter (nCBFintratumoral and nCBFperitumoral, respectively). Visual grading scales and quantitative parameters between GBM and brain metastasis were compared. In addition, the area under the receiver-operating characteristic curve was used to evaluate the diagnostic performance of ASL-driven CBF to differentiate GBM from brain metastasis.For qualitative analysis, GBM group showed significantly higher grade compared to metastasis group (p = 0.001). For quantitative analysis, both nCBFintratumoral and nCBFperitumoral in GBM were significantly higher than those in metastasis (both p < 0.001). The areas under the curve were 0.677, 0.714, and 0.835 for visual grading, nCBFintratumoral, and nCBFperitumoral, respectively (all p < 0.001).ASL perfusion MR imaging can aid in the differentiation of GBM from brain metastasis.

The purpose of our study was to determine the frequency and severity of intracerebral hemorrhages and T2 hyperintense white matter lesions (WMLs) following radiation therapy for brain tumors in adult patients. Of 648 adult brain tumor patients who received radiation therapy at our institute, magnetic resonance (MR) image data consisting of a gradient echo (GRE) and FLAIR T2-weighted image were available three and five years after radiation therapy in 81 patients. Intracerebral hemorrhage was defined as a hypointense dot lesion appearing on GRE images after radiation therapy. The number and size of the lesions were evaluated. The T2 hyperintense WMLs observed on the FLAIR sequences were graded according to the extent of the lesion. Intracerebral hemorrhage was detected in 21 (25.9%) and 35 (43.2) patients in the three- and five-year follow-up images, respectively. The number of intracerebral hemorrhages per patient tended to increase as the follow-up period increased, whereas the size of the intracerebral hemorrhages exhibited little variation over the course of follow-up. T2 hyperintense WMLs were observed in 27 (33.3%) and 32 (39.5) patients in the three and five year follow-up images, respectively. The age at the time of radiation therapy was significantly higher (p < 0.001) in the patients with T2 hyperintense WMLs than in those without lesions. Intracerebral hemorrhages are not uncommon in adult brain tumor patients undergoing radiation therapy. The incidence and number of intracerebral hemorrhages increased over the course of follow-up. T2 hyperintense WMLs were observed in more than one-third of the study population.

The recent blood flow and magnetization transfer (MT) technique termed alternate ascending/descending directional navigation (ALADDIN) achieves the contrast using interslice blood flow and MT effects with no separate preparation RF pulse, thereby potentially overcoming limitations of conventional methods. In this study, we examined the signal characteristics of ALADDIN as a simultaneous blood flow and MT imaging strategy, by comparing it with pseudo-continuous ASL (pCASL) and conventional MT asymmetry (MTA) methods, all of which had the same bSSFP readout. Bloch-equation simulations and experiments showed ALADDIN perfusion signals increased with flip angle, whereas MTA signals peaked at flip angle around 45°-60°. ALADDIN provided signals comparable to those of pCASL and conventional MTA methods emulating the first, second, and third prior slices of ALADDIN under the same scan conditions, suggesting ALADDIN signals to be superposition of signals from multiple labeling planes. The quantitative cerebral blood flow signals from a modified continuous ASL model overestimated the perfusion signals compared to those measured with a pulsed ASL method. Simultaneous mapping of blood flow, MTA, and MT ratio in the whole brain is feasible with ALADDIN within a clinically reasonable time, which can potentially help diagnosis of various diseases.

We present a new method for magnetization transfer (MT) ratio imaging in the brain that requires no separate saturation pulse. Interslice MT effects that are inherent to multi-slice balanced steady-state free precession (bSSFP) imaging were controlled via an interslice delay time to generate MT-weighted (0 s delay) and reference images (5-8 s delay) for MT ratio (MTR) imaging of the brain. The effects of varying flip angle and phase encoding (PE) order were investigated experimentally in normal, healthy subjects. Values of up to ∼50% and ∼40% were observed for white and gray matter MTR. Centric PE showed larger MTR, higher SNR, and better contrast between white and gray matter than linear PE. Simulations of a two-pool model of MT agreed well with in vivo MTR values. Simulations were also used to investigate the effects of varying acquisition parameters, and the effects of varying flip angle, PE steps, and interslice delay are discussed. Lastly, we demonstrated reduced banding with a non-balanced SSFP-FID sequence and showed preliminary results of interslice MTR imaging of meningioma.

PurposeTo assess the prognosis predictability of a measurable enhancing lesion using histogram parameters produced by the normalized cerebral blood volume (nCBV) and normalized apparent diffusion coefficient (nADC) after completion of standard concomitant chemoradiotherapy (CCRT) and adjuvant temozolomide (TMZ) medication in glioblastoma multiforme (GBM) patients.Materials and methodsThis study was approved by the institutional review board (IRB), and the requirement for informed consent was waived. A total of 59 patients with newly diagnosed GBM who received standard CCRT with TMZ and adjuvant TMZ for six cycles underwent perfusion-weighted and diffusion-weighted imaging. Twenty-seven patients had a measurable enhancing lesion and 32 patients lacked a measurable enhancing lesion based on the Response Assessment in Neuro-Oncology (RANO) criteria in the follow-up MRI, which was performed within 3 months after adjuvant TMZ therapy was completed. We measured the nCBV and nADC histogram parameters based on the measurable enhancing lesion. The progression free survival (PFS) was analyzed by the Kaplan-Meier method with the use of the log-rank test.ResultsThe median PFS of patients lacking measurable enhancing lesion was longer than for those with measurable enhancing lesions (17.6 vs 3.3 months, PConclusionWe found that the nCBV value can be used for the prognosis prediction of a measurable enhancing lesion after the completion of standard treatment for GBM, wherein a high 99th percentile nCBV value (≧ 4.5) suggests a better PFS for GBM patients.

Accurate diagnosis of lymph node metastasis is crucial in treatment planning for cancer patients. Despite the use of various parameters, making correct diagnosis of a small metastatic or a hyperplastic benign node is still a challenge. In this study, we evaluated the feasibility of detecting lymph node metastasis using a new ultrasmall superparamagnetic iron oxide particle, PJY10, in a rabbit model.To make metastatic and benign lymph nodes, either VX2 carcinoma or fecal material suspension was inoculated into thighs of 56 rabbits three weeks or three days before magnetic resonance (MR) imaging, respectively. T2*-weighted 3T MR imaging was performed before and 24 hours after PJY10 injection (5.2 [n = 15], 7.8 [n = 17], and 10.4 [n = 24] mg Fe/kg). MR images were correlated with pathologic results to calculate sensitivity and specificity. Quantitative analysis of the signal intensity (SI)--number of voxels[low] (the fraction of the number of voxels with the normalized SI on the postcontrast image lower than that on the precontrast image) and mean SI ratio--was also performed for each lymph node.Sensitivities were 100% at all three dosages, whereas specificity increased with increasing dosage (89% at 10.4 mg Fe/kg). The benign nodes had a significantly higher number of voxels[low] and a lower mean SI ratio than the metastatic nodes at the dosage of 10.4 mg Fe/kg (P

PURPOSE: To evaluate whether adding a contrast-enhanced fluid-attenuated inversion recovery (FLAIR) sequence to routine magnetic resonance imaging (MRI) can detect additional abnormalities in the brains of symptomatic patients with mild traumatic brain injury. MATERIALS AND METHODS: Fifty-four patients with persistent symptoms following mild closed head injury were included in our retrospective study (M ∶ F = 32 ∶ 22, mean age: 59.8 ± 16.4, age range: 26-84 years). All MRI examinations were obtained within 14 days after head trauma (mean: 3.2 ± 4.1 days, range: 0.2-14 days). Two neuroradiologists recorded (1) the presence of traumatic brain lesions on MR images with and without contrast-enhanced FLAIR images and (2) the pattern and location of meningeal enhancement depicted on contrast-enhanced FLAIR images. The number of additional traumatic brain lesions diagnosed with contrast-enhanced FLAIR was recorded. Correlations between meningeal enhancement and clinical findings were also evaluated. RESULTS: Traumatic brain lesions were detected on routine image sequences in 25 patients. Three additional cases of brain abnormality were detected with the contrast-enhanced FLAIR images. Meningeal enhancement was identified on contrast-enhanced FLAIR images in 9 cases while the other routine image sequences showed no findings of traumatic brain injury. Overall, the additional contrast-enhanced FLAIR images revealed more extensive abnormalities than routine imaging in 37 cases (p

BACKGROUND AND PURPOSE: To apply a texture analysis of apparent diffusion coefficient (ADC) maps to evaluate glioma heterogeneity, which was correlated with tumor grade. MATERIALS AND METHODS: Forty patients with glioma (WHO grade II (n = 8), grade III (n = 10) and grade IV (n = 22)) underwent diffusion-weighted imaging (DWI), and the corresponding ADC maps were obtained. Regions of interest containing the lesions were drawn on every section of the ADC map containing the tumor, and volume-based data of the entire tumor were constructed. Texture and first order features including entropy, skewness and kurtosis were derived from the ADC map using in-house software. A histogram analysis of the ADC map was also performed. The texture and histogram parameters were compared between low-grade and high-grade gliomas using an unpaired student's t-test. Additionally, a one-way analysis of variance analysis with a post-hoc test was performed to compare the parameters of each grade. RESULTS: Entropy was observed to be significantly higher in high-grade gliomas than low-grade tumors (6.861±0.539 vs. 6.261±0.412, P = 0.006). The fifth percentiles of the ADC cumulative histogram also showed a significant difference between high and low grade gliomas (836±235 vs. 1030±185, P = 0.037). Only entropy proved to be significantly different between grades III and IV (6.295±0.4963 vs. 7.119±0.3165, P

To evaluate the usefulness of dynamic susceptibility contrast (DSC) enhanced perfusion MR imaging in predicting major genetic alterations in glioblastomas.Twenty-five patients (M:F = 13∶12, mean age: 52.1±15.2 years) with pathologically proven glioblastoma who underwent DSC MR imaging before surgery were included. On DSC MR imaging, the normalized relative tumor blood volume (nTBV) of the enhancing solid portion of each tumor was calculated by using dedicated software (Nordic TumorEX, NordicNeuroLab, Bergen, Norway) that enabled semi-automatic segmentation for each tumor. Five major glioblastoma genetic alterations (epidermal growth factor receptor (EGFR), phosphatase and tensin homologue (PTEN), Ki-67, O6-methylguanine-DNA methyltransferase (MGMT) and p53) were confirmed by immunohistochemistry and analyzed for correlation with the nTBV of each tumor. Statistical analysis was performed using the unpaired Student t test, ROC (receiver operating characteristic) curve analysis and Pearson correlation analysis.The nTBVs of the MGMT methylation-negative group (mean 9.5±7.5) were significantly higher than those of the MGMT methylation-positive group (mean 5.4±1.8) (p = .046). In the analysis of EGFR expression-positive group, the nTBVs of the subgroup with loss of PTEN gene expression (mean: 10.3±8.1) were also significantly higher than those of the subgroup without loss of PTEN gene expression (mean: 5.6±2.3) (p = .046). Ki-67 labeling index indicated significant positive correlation with the nTBV of the tumor (p = .01).We found that glioblastomas with aggressive genetic alterations tended to have a high nTBV in the present study. Thus, we believe that DSC-enhanced perfusion MR imaging could be helpful in predicting genetic alterations that are crucial in predicting the prognosis of and selecting tailored treatment for glioblastoma patients.

PURPOSE: To compare the reproducibilities of manual and semiautomatic segmentation method for the measurement of normalized cerebral blood volume (nCBV) using dynamic susceptibility contrast-enhanced (DSC) perfusion MR imaging in glioblastomas. MATERIALS AND METHODS: Twenty-two patients (11 male, 11 female; 27 tumors) with histologically confirmed glioblastoma (WHO grade IV) were examined with conventional MR imaging and DSC imaging at 3T before surgery or biopsy. Then nCBV (means and standard deviations) in each mass was measured using two DSC MR perfusion analysis methods including manual and semiautomatic segmentation method, in which contrast-enhanced (CE)-T1WI and T2WI were used as structural imaging. Intraobserver and interobserver reproducibility were assessed according to each perfusion analysis method or each structural imaging. Interclass correlation coefficient (ICC), Bland-Altman plot, and coefficient of variation (CV) were used to evaluate reproducibility. RESULTS: Intraobserver reproducibilities on CE-T1WI and T2WI were ICC of 0.74-0.89 and CV of 20.39-36.83% in manual segmentation method, and ICC of 0.95-0.99 and CV of 8.53-16.19% in semiautomatic segmentation method, repectively. Interobserver reproducibilites on CE-T1WI and T2WI were ICC of 0.86-0.94 and CV of 19.67-35.15% in manual segmentation method, and ICC of 0.74-1.0 and CV of 5.48-49.38% in semiautomatic segmentation method, respectively. Bland-Altman plots showed a good correlation with ICC or CV in each method. The semiautomatic segmentation method showed higher intraobserver and interobserver reproducibilities at CE-T1WI-based study than other methods. CONCLUSION: The best reproducibility was found using the semiautomatic segmentation method based on CE-T1WI for structural imaging in the measurement of the nCBV of glioblastomas.

BACKGROUND: Glioma grading assumes significant importance in that low- and high-grade gliomas display different prognoses and are treated with dissimilar therapeutic strategies. The objective of our study was to retrospectively assess the usefulness of a cumulative normalized cerebral blood volume (nCBV) histogram for glioma grading based on 3 T MRI. METHODS: From February 2010 to April 2012, 63 patients with astrocytic tumors underwent 3 T MRI with dynamic susceptibility contrast perfusion-weighted imaging. Regions of interest containing the entire tumor volume were drawn on every section of the co-registered relative CBV (rCBV) maps and T2-weighted images. The percentile values from the cumulative nCBV histograms and the other histogram parameters were correlated with tumor grades. Cochran's Q test and the McNemar test were used to compare the diagnostic accuracies of the histogram parameters after the receiver operating characteristic curve analysis. Using the parameter offering the highest diagnostic accuracy, a validation process was performed with an independent test set of nine patients. RESULTS: The 99th percentile of the cumulative nCBV histogram (nCBV C99), mean and peak height differed significantly between low- and high-grade gliomas (P =

BACKGROUND: Cancer stem cells (CSCs) are highly tumorigenic and are responsible for tumor progression and chemoresistance. Noninvasive imaging methods for the visualization of CSC populations within tumors in vivo will have a considerable impact on the development of new CSC-targeting therapeutics. METHODOLOGY/PRINCIPAL FINDINGS: In this study, human breast cancer stem cells (BCSCs) transduced with dual reporter genes (human ferritin heavy chain [FTH] and enhanced green fluorescence protein [EGFP]) were transplanted into NOD/SCID mice to allow noninvasive tracking of BCSC-derived populations. No changes in the properties of the BCSCs were observed due to ferritin overexpression. Magnetic resonance imaging (MRI) revealed significantly different signal intensities (R(2)* values) between BCSCs and FTH-BCSCs in vitro and in vivo. In addition, distinct populations of pixels with high R(2)* values were detected in docetaxel-treated FTH-BCSC tumors compared with control tumors, even before the tumor sizes changed. Histological analysis revealed that areas showing high R(2)* values in docetaxel-treated FTH-BCSC tumors by MRI contained EGFP+/FTH+ viable cell populations with high percentages of CD44+/CD24- cells. CONCLUSIONS/SIGNIFICANCE: These findings suggest that ferritin-based MRI, which provides high spatial resolution and tissue contrast, can be used as a reliable method to identify viable cell populations derived from BCSCs after chemotherapy and may serve as a new tool to monitor the efficacy of CSC-targeting therapies in vivo.

BACKGROUND: Due to the ability of macrophages to specifically home to tumors, their potential use as a delivery vehicle for cancer therapeutics has been suggested. Tracking the delivery and engraftment of macrophages into human tumors with a 1.5T clinical MR scanner requires the development of sensitive contrast agents for cell labeling. Therefore, this study aimed to determine whether intravenously injected macrophages could target a primary tumor as well as metastatic LNs, and whether these cells could be detected in vivo by MRI. METHODOLOGY: Peritoneal macrophages were obtained from BALB/c nude mice. The viability, phagocytotic capacity and migratory activity of the macrophages were assessed. MR imaging was performed using a clinical 1.5 T MR scanner and we estimated the T2* of the labeled macrophages. Metastatic lymph nodes were produced in BALB/c nude mice. We administrated 2×10⁶ macrophages labeled with 50 µg Fe/mL FIONs intravenously into the mice. In the 3D T2* GRE MR images obtained one day after the injection of the labeled macrophages or FION solution, the percentages of pixels in the tumors or LNs below the minimum normalized SI (signal intensity) threshold were summated and reported as the black pixel count (%) for the FION hypointensity. Tumors in the main tumor model as well as the brachial, axillary and inguinal lymph nodes in the metastatic LN models were removed and stained. For all statistical analyses, single-group data were assessed using t test or the Mann-Whitney test. Repeated measurements analysis of variance (ANOVA) with Tukey-Kramer post hoc comparisons were performed for multiple comparisons. CONCLUSIONS: The FION-labeled macrophages, which could be non-invasively monitored using a 1.5T clinical MR scanner, targeted both the main tumors and LN metastases. Overall, the results of this study suggest that the use of macrophages may have many future applications in the clinic for vectorizing therapeutic agents toward main tumors as well as LN metastases.

Despite its superior soft tissue contrast and non-invasive nature, MRI requires long scan times due to its intrinsic signal acquisition principles, a main drawback which technological advancements in MRI have been focused on. In particular, scan time reduction is a natural requirement in neuroimaging due to detailed structures requiring high resolution imaging and often volumetric (3D) acquisitions, and numerous studies have recently attempted to harness deep learning (DL) technology in enabling scan time reduction and image quality improvement. Various DL-based image reconstruction products allow for additional scan time reduction on top of existing accelerated acquisition methods without compromising the image quality. [ABSTRACT FROM AUTHOR]